Article
Engineering, Chemical
Elnaz Shahbazali, Emilie M. F. Billaud, Arash Sarhangi Fard, Jan Meuldijk, Guy Bormans, Timothy Noel, Volker Hessel
Summary: This study successfully achieved the separation and enrichment of trans-cyclooctene through reaction and adsorption in micro-flow. The closed-loop recycling-flow presented a systemic approach to increase product yield effectively.
Article
Electrochemistry
Kazuhiro Okamoto, Naoki Shida, Mahito Atobe
Summary: In this study, the electrochemical [3+2] cycloaddition of phenols and alkenes was successfully achieved in a laminar-flow microreactor at an unprecedentedly low electrolyte concentration. The optimization of the reactor configuration prevented the overoxidation of the resulting cycloadducts, and nine dihydrobenzofuran derivatives were synthesized without any oxidant. Additionally, a simple scale-up was enabled by using a parallel stacked flow cell system.
Article
Chemistry, Applied
Jean-Paul Kestemont, James R. Frost, Jerome Jacq, Patrick Pasau, Frederic Perl, Julien Brown, Matthieu Tissot
Summary: We present a large-scale carboxylation of N-Boc-4,4-difluoropiperidine (1) enabled by a continuous flow process. The flow process involved N-Boc-directed alpha-deprotonation using s-BuLi in THF and subsequent trapping with CO2 gas. Flow chemistry allowed for safe and scalable preparation of 400 g of carboxylic acid 2 in a day to support our medicinal chemistry research program.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Review
Engineering, Multidisciplinary
Siyuan Zheng, Junyu Yan, Kai Wang
Summary: Electrochemical methods have unique advantages in organic chemical synthesis, but face limitations due to complex transport issues. The application of microreaction technology in electrosynthesis has enabled efficient, successive, and easily scaled-up technologies. Further research is needed to clarify scientific rules and engineering features in microreactors for the development of novel electrosynthesis technology.
Article
Chemistry, Multidisciplinary
Masahiro Takumi, Hodaka Sakaue, Aiichiro Nagaki
Summary: A novel flow electrochemical reactor has been developed to achieve electrolysis within a few seconds and enable reaction with nucleophiles before the decomposition of short-lived carbocations. Furthermore, continuous operation based on this system allows for rapid synthesis of pharmaceutical precursors on demand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Engineering, Environmental
Chenghao Zhang, Jing Luo, Binqi Xie, Wei Liu, Jisong Zhang
Summary: A continuous micro-packed bed reactor platform is developed to determine the kinetics of aerobic ethylbenzene oxidation in the presence of N-hydroxyphthalimide. The reactor system offers enhanced gas-liquid mass transfer, leading to a significant increase in the space-time yield of ethylbenzene oxidation compared to traditional batch reactors. Furthermore, the organic catalyst NHPI is covalently anchored on commercial activated carbon through an imidization reaction. The synthesized heterogeneous catalysts exhibit excellent performance in terms of acetophenone yield and turnover frequency (TOF).
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Chemistry, Organic
Marco Colella, Pantaleo Musci, Debora Cannillo, Mauro Spennacchio, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Summary: This study reports the generation and functionalization of two different lithiated four-membered aza-heterocycles under continuous flow conditions. Flow technology, along with cyclopentylmethyl ether as a solvent, enables easy handling of lithiated intermediates and addresses sustainability concerns. The use of N-Boc-3-iodoazetidine as a common synthetic platform allows the genesis of C3-lithiated azetidine and C2-lithiated azetine depending on the lithiation agent.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Merlin Kleoff, Lisa Boeser, Linda Baranyi, Philipp Heretsch
Summary: A metal-free synthesis method for benzotriazoles in flow using azides and in situ generated arynes is reported. The modular access to benzotriazoles is provided by employing different substitution patterns of the azide and aryne coupling partners. The safety profile of the process is improved by minimizing thermal strain of hazardous azides and accumulation of reactive intermediates through short reaction times in flow. The scalability of the reaction is also demonstrated.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ankit Kumar Mittal, Gaurav Prakash, Pramod Pathak, Debabrata Maiti
Summary: This paper describes a flow chemistry approach for synthesizing high-energy molecules CTA and DNAN, and scaling them up to multi-gram scale using an automated flow reactor system. The method offers a high degree of safety and scalability compared to conventional syntheses. The optimized processes achieved high yield and short reaction times. The results suggest that this method is suitable for the safe production of CTA and DNAN at a multi-gram scale in the laboratory.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Dimitris I. Ioannou, Luca Capaldo, Jiri Sanramat, Joost N. H. Reek, Timothy Noel
Summary: Electrophotocatalysis plays a significant role in organic synthesis and has potential for scalability. This study introduces a new concept of a flow reactor that utilizes both photons and electrons simultaneously. The device is not only applicable for electrophotocatalysis, but also for purely electrochemical and photochemical reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Pantaleo Musci, Timo von Keutz, Ferdinand Belaj, Leonardo Degennaro, David Cantillo, C. Oliver Kappe, Renzo Luisi
Summary: A telescoped continuous flow protocol for the generation, lithiation, and electrophilic trapping of 1-azabicyclo[1.1.0]butanes has been reported, showcasing its efficiency with over 20 examples. The flow method allows for exquisite control of reaction parameters and operates at higher temperatures and safer conditions compared to batch mode.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Engineering, Environmental
Yiran Cao, Natan Padoin, Cintia Soares, Timothy Noe
Summary: A comprehensive understanding of the underlying phenomena is crucial for the design and analysis of chemical reactors for multiphase electro-organic transformations. The study shows that operating at high concentrations of rate-limiting species is beneficial, but excessively high concentrations may not improve mass transfer and current/voltage relation. Keeping an internal:external phase electrical conductivity ratio > 1, working at lower velocities, and operating at higher cell potentials contribute to improved reactor performance.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Jiyizhe Zhang, Naoto Sugisawa, Kobi C. Felton, Shinichiro Fuse, Alexei A. Lapkin
Summary: In this study, the Schotten-Baumann reaction was optimized using a Bayesian optimization algorithm based on the q-noisy expected hypervolume improvement (qNEHVI) acquisition function. The undesired hydrolysis was successfully suppressed by conducting the reaction under flow conditions. The relationship between solvent and flow rate was discussed to gain more insights into this reaction.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Engineering, Chemical
Paulo Victor Cuesta Calvo, Patrick Rodrigues Batista, Renan Rodrigues de Oliveira Silva, Attilio Converti, Saleh Al Arni, Carlo Solisio, Lucas C. Ducati, Mauri Sergio Alves Palma
Summary: Microreactor technology is increasingly used in the chemical-pharmaceutical industry for safer and more efficient drug production compared to traditional batch processes. In a study on the production of the first intermediate in rosiglitazone synthesis, a single microreactor chip was able to outperform more than five batch reactors under optimal conditions. Kinetic analysis revealed a second-order reaction, and thermodynamic parameters were determined through the Eyring equation and DFT calculations, supporting a concerted nucleophilic aromatic substitution reaction mechanism.
CHEMICAL ENGINEERING & TECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ji-Ho Kang, Gwang-Noh Ahn, Heekwon Lee, Se-Jun Yim, Santosh Lahore, Hyune-Jea Lee, Heejin Kim, Ji Tae Kim, Dong-Pyo Kim
Summary: The study achieved subsecond synthesis of drug scaffolds through the use of a system with 16 numbered-up printed metal microreactor components. By scaling up and integrating single microreactor units, larger-scale production of pharmaceutical compounds was successfully realized.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Yusuke Kuroda, Shingo Harada, Akinori Oonishi, Yousuke Yamaoka, Ken-ichi Yamada, Kiyosei Takasu
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2015)
Article
Chemistry, Multidisciplinary
Manabu Sato, Hiroki Azuma, Akihiro Daigaku, Sota Sato, Kiyosei Takasu, Kentaro Okano, Hidetoshi Tokuyama
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2017)
Article
Chemistry, Multidisciplinary
Yusuke Kuroda, Shingo Harada, Akinori Oonishi, Hiroki Kiyama, Yousuke Yamaoka, Ken-ichi Yamada, Kiyosei Takasu
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2016)
Review
Chemistry, Medicinal
Kiyosei Takasu
CHEMICAL & PHARMACEUTICAL BULLETIN
(2016)
Review
Chemistry, Multidisciplinary
Kiyosei Takasu
ISRAEL JOURNAL OF CHEMISTRY
(2016)
Article
Chemistry, Organic
Yinli Wang, Raphael Oriez, Satoru Kuwano, Yousuke Yamaoka, Kiyosei Takasu, Ken-ichi Yamada
JOURNAL OF ORGANIC CHEMISTRY
(2016)
Article
Chemistry, Organic
Ken-ichi Yamada, Yusuke Matsumoto, Shintaro Fujii, Takehito Konishi, Yousuke Yamaoka, Kiyosei Takasu
JOURNAL OF ORGANIC CHEMISTRY
(2016)
Article
Chemistry, Organic
Ken-ichi Yamada, Akinori Oonishi, Yusuke Kuroda, Shingo Harada, Hiroki Kiyama, Yousuke Yamaoka, Kiyosei Takasu
TETRAHEDRON LETTERS
(2016)
Article
Chemistry, Organic
Yinli Wang, Raphael Oriez, Shougun Ou, Yasunori Miyakawa, Yousuke Yamaoka, Kiyosei Takasu, Ken-Ichi Yamada
Article
Chemistry, Organic
Naoki Ogawa, Yousuke Yamaoka, Ken-ichi Yamada, Kiyosei Takasu
Article
Chemistry, Organic
Yousuke Yamaoka, Motoki Ueda, Tohru Yamashita, Kazuma Shimoda, Ken-ichi Yamada, Kiyosei Takasu
TETRAHEDRON LETTERS
(2017)
Review
Chemistry, Organic
Naoya Shindo, Kiyosei Takasu
Article
Chemistry, Medicinal
Norihito Arichi, Shinichi Fujiwara, Michiyasu Ishizawa, Makoto Makishima, Duy H. Hua, Ken-ichi Yamada, Yousuke Yamaoka, Kiyosei Takasu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Multidisciplinary
Bubwoong Kang, Yinli Wang, Satoru Kuwano, Yousuke Yamaoka, Kiyosei Takasu, Ken-ichi Yamada
CHEMICAL COMMUNICATIONS
(2017)
Review
Chemistry, Organic
Yusuke Kuroda, Shingo Harada, Ken-ichi Yamada, Kiyosei Takasu
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN
(2018)
